MSH2 stimulates interfering and inhibits non-interfering crossovers in response to genetic polymorphism

Abstract In Arabidopsis, local sequence polymorphism between homologs can stimulate double-strand break (DSB) repair via crossover formation in a MSH2-dependent manner. To understand how MSH2 regulates crossovers formed by the independent interfering and non-interfering pathways, we combine mutants that elevate non-interfering crossovers with msh2 . We demonstrate that MSH2 blocks non-interfering crossovers at polymorphic loci, which is the opposite effect to interfering crossovers. We also observe MSH2-independent crossover inhibition at highly polymorphic sites. We measure recombination along the chromosome arms, in lines differing in the heterozygosity pattern, and observe a dramatic crossover increase at the boundaries between heterozygous and homozygous regions, which is MSH2-dependent. Together, we show that MSH2 is a master regulator of meiotic DSB repair, with antagonistic effects on interfering and non-interfering crossovers, that shapes the crossover landscape in relation to interhomolog polymorphism.